Marked increases in hippocampal neuron indoleamine 2, 3-dioxygenase via IFN-γ-independent pathway following transient global ischemia in mouse

Indoleamine 2, 3-dioxygenase (IDO), which catabolizes L-tryptophan (L-TRP) to L-kynurenine (L-KYN), is an immunoregulatory factor that is up-regulated via an interferon-gamma (IFN-γ)-dependent and/or -independent mechanism. In this study, we investigated the localization of IDO and whether induction of IDO expression is an IFN-γ-dependent and/or -independent mechanism in the CNS after cerebral ischemia. The expressions of IDO protein and mRNA were investigated at different time points following cerebral ischemia using immunohistochemistry, immunofluorescence and RT-PCR. Hippocampal neuron IDO mRNA and immunohistochemical staining were significantly up-regulated 72 h after transient global ischemia. Although IFN-γ is a dominant inducer of IDO, hippocampal neuron IDO was clearly up-regulated in IFN-γ KO mice. In summary, this is the first finding that up-regulation of IDO in hippocampal neurons after transient global ischemia occurs via INF-γ-independent mechanisms.